The section continues to investigate pharmacological and behavioral treatments of substance abuse and to explore combinations of treatments. We have already demonstrated the effectiveness of behavioral interventions (reinforcement of cocaine-negative urine samples) in large inner-city samples of intravenous polydrug abusers, and we continue to evaluate the best ways to apply the treatment. In the past year we completed the active-treatment phase of a study to address the question of how a hypothetical methadone-maintenance clinic could best allocate its resources (both pharmacological and nonpharmacological) to reduce both heroin and cocaine abuse, if the clinic were to institute voucher-based contingency management. By combining an intervention primarily aimed at decreasing cocaine use through behavioral reinforcement (contingency management) with another intervention focused on decreasing illicit-opiate use through pharmacological treatment (high-dose methadone maintenance), we hypothesize that we will see greater abstinence from cocaine and illicit opiates than has been seen when either approach was applied separately. Analyses are ongoing. In the interest of cost containment and technology transfer, we are conducting pilot studies in which the reinforcers are lottery draws rather than vouchers, since work by others has shown that a lottery-based reinforcement procedure can be funded by donations from community manufacturers and merchants. The initial pilot study indicated that the lottery procedure generated substantial enthusiasm among study participants and is technically easier than the voucher program. In a further ongoing pilot study we are comparing two different lottery procedures and two different densities of reinforcement. We plan to incorporate the lottery procedure into a more ambitious study in which a variety of low- or no-cost incentives are targeted toward a broad range of behavioral changes beyond reductions in drug use. Another current focus of our research derives from laboratory-animal data showing that stress-induced reinstatement of cocaine-seeking and/or heroin-seeking can be prevented with the alpha-adrenergic agonist lofexidine. In the past year we completed a dose-ranging study to determine how lofexidine can most safely be co-administered with methadone in humans. We plan to follow this with a clinical trial in which voucher-initiated abstinence is followed by maintenance on lofexidine (or placebo) for prevention of stress-induced relapse.